The expression of a normal immune response is subject to a variety of genetic controls. The principle objective of this work is to determine the nature and mechanism of these genetic controls and to study their involvement in two abnormal expressions of immune cells, plasmacytoma formation and autoimmune disease. This work accordingly involves several aspects of normal, autoimmune, and malignant lymphoid cell expression. (1) with a view to considering aspects of the normal immune response that are relevant to either plasmacytoma formation or autoimmunity, our continuing studies in this area will principally concern (a) Control of IgA differentiation- concepts of local peripheral differentiation versus selective homing; (b) Immune response genes - estimates of number of loci controlling responses to various antigens in mice, particularly myeloma proteins and bacterial antigens in allotype congenic mice; (c) Structural studies of mouse myeloma proteins derived from different allotype backgrounds. (2) analysis of anti-RBC autoantibody production in NZ mice. Our previous concept of two gene control will be followed with NZC mice that carry only one of these genes, and also appear to have immunologic abnormalities. Evidence of immune response gene action in autoimmunity will be sought in the spontaneous and induced models. Autoantibody populations will be examined for direct evidence of restricted origin using allotype studies. (3) Further selective breeding of mice will be used to study possible associations of susceptibility to plasmacytoma induction and autoimmunity. Allotype congenic, tetraparental, and a range of inbred strains will be studied for susceptibility to plasmacytoma induction.